The immediate goal of these studies is to develop methods for efficiency introducing human globin genes into hemopoietic cells both from tissue culture lines and normal bone marrow to study their tissue specific regulation. We have constructed a hybrid SV40 virus which contains the prokaryotic gene coding for chloramphenicol acetyl transferase (CAT) and have obtained gene transfer and transient expression of CAT in a large number of fibroblast and hemopoietic cell lines of both mouse and human origin and in normal fresh bone marrow cells of mouse, monkey and man. The results with suspension hemopoietic cell lines and fresh bone marrow cells represent a significance advance over the low or undetectable levels of gene transfer obtained with the CaPO4 precipitate technique. We have also constructed an SV40 recombinant containing the methotrexate resistant DHFR coding sequence and have successfully used this viral lysate to transform CHO DG21 cells that lack both DHFR genes. Recombinant SV40 lysates contain wild type SV40 virus that severely compromises their use as viral vectors. We have therefore made use of helper free recombinant adenoviruses that contain the neomycin resistant gene and have successfully transformed both K562, MEL and various fibroblast cell lines to G418 resistance. In K562 cells 1-3 copies of the whole virus are found to be integrated. As the transformation frequency of adenovirus in K562 and MEL cells is higher than that of calcium phosphate, mediated DNA transfer, viral vectors will be constructed to facilitate introduction of a selectable gene and a human globin gene into both hematopoietic cell lines in vitro and normal hematopoietic stem cells in vivo.